Many commercially important proteins are produced in recombinantly engineered cells that have been adapted for long term growth in culture. Frequently, the proteins are expressed as a single polypeptide chain. Also expressed in these cells are multiple heterologous polypeptides that can associate to form heteromeric complexes, such as for example, an antibody, which is formed by the expression of equal parts of heavy chains and light chains.
One difficulty that can be encountered when expressing heteromeric complexes in cells is obtaining appropriate amounts of each of the recombinant polypeptides that form a component of the complex. For example, in the expression of an antibody frequently either the heavy chain or the light chain are expressed to relatively high levels with respect to the corresponding partner; however, obtaining a cell line expressing both chains to high levels and in roughly equal amounts is difficult.
These difficulties result in additional steps and also repetition of steps in the process of generating cell lines expressing recombinant polypeptides resulting in delays which also substantially increase costs associated with recombinant expression of the polypeptides. Thus, there is a need in the art for simpler methods of selecting for high level expression of polypeptides in cell cultures so as to increase production of the polypeptides thereby reducing the cost and time investment necessary for selection of cells expressing the polypeptides. The invention fulfills this need by providing an improved method for selecting cells expressing polypeptides.